The present invention generally relates to methods for treating disorders characterized by the formation of tumors, including cancer.
Loss of normal control of cellular proliferation results in unregulated cell growth and, often, the formation of cellular masses commonly known as tumors. Tumors may be malignant or non-malignant. The cells composing malignant tumors often exhibit a lack of normal differentiation and possess the ability to invade local tissues and metastasize, whereas in non-malignant tumors the mass of cells is generally localized. Malignant tumors can develop in any organ at any age and, even with treatment, often result in the death of the subject. While not typically posing a threat to life, non-malignant tumors can impose severe restrictions on normal physiological function.
Tumors are typically treated by surgical removal, radiation, and/or chemotherapy. Surgery is the oldest effective form of tumor therapy and can often result in a complete cure, depending of the type and nature of the tumor. Many tumors, however, occur in locations and/or number that make surgery impossible or impractical. Also, surgical debulking is not guaranteed to remove all abnormal cells, particularly in the case of tumors located in the brain where maximum preservation of normal tissue is desired. Residual abnormal cells pose an increased risk of tumor re-growth and/or metastasis.
Radiation therapy is often used as an adjunct to surgery. Various types of radiation, both from external and implanted sources, have been used with some success. Low linear-energy-transfer (LET) sources, such as beta particles and gamma rays, require the presence of oxygen for their pharmacologic activity. Many tumors, however, are hypoxic due to reduced collateral blood vessel growth into the tumor interstitia, limiting the effectiveness of low LET sources and requiring repeated treatments over extended periods of time to produce any significant reduction in tumor cells.
High LET sources, such as neutrons, do not require oxygen to be effective. External beam, fast neutron therapy was widely tested in the 1970s (see, for example, Laramore, et al, Cancer 42:96-103, 1978 and Catteral and Bentley, Fast neutrons in the treatment of cancer, New York, Brune and Stratton, 1979). Unfortunately, significant radiation damage occurred to normal tissues, and patients often died from widespread radiation-induced necrosis.
Brachytherapy using an implantable neutron source has been used as an alternative to external beams. Many neutron-emitting isotopes are unsuitable for brachytherapy, however, because of short half lives and low energy. The transplutonium radioactive isotope californium-252 (252Cf) is an exception, having a half-life of 2.6 years and emitting fast neutrons with an average energy of 2.3 MeV. While this technique has shown some promise in the treatment of a small number of tumor types, notably those found in the cervix or oral cavity, the relatively large size of the neutron source has limited the use of this technique.
Accordingly, there is a need in the art for new methods of treating tumors using neutrons. The present invention addresses that need.
The present invention overcomes many of the problems in the art by providing a method of treating a subject having a disorder characterized by the presence of one or more tumors comprising inserting a miniaturized concentrated neutron emitting source into said tumor(s) for a time sufficient to irradiate the cells of the tumor(s). The invention method can be employed in the treatment of both malignant and non-malignant tumors and is especially useful in the treatment of malignant tumors found in the brain, cervix, oral cavity, esophagus, prostate, and other internal organs. A preferred neutron source is californium-252. In one alternative embodiment of the invention, the majority of the tumor can be surgically removed prior to insertion of the miniaturized neutron emitting source. In a further embodiment of the invention, a neutron capture compound can be localized to the cells of the tumor prior to insertion of the miniaturized neutron emitting source in order to augment the effects of neutron therapy.